Brain-derived neurotrophic factor (BDNF) determines a sex difference in cue-conditioned alcohol seeking in rats

• Published in: Behavioural brain research 2018-02, Vol.339, p.73-78
• Main Authors: Hogarth, Samuel J., Jaehne, Emily J., van den Buuse, Maarten, Djouma, Elvan
• Format: Article
• Language: English
• Subjects: Alcohol seeking; Animals; Behavior, Addictive - physiopathology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cocaine - administration & dosage; Cocaine - pharmacology; Conditioning, Operant - drug effects; Extinction; Extinction, Psychological - drug effects; Rats, Sprague-Dawley; Reinstatement; Self Administration; Sex Characteristics; Sex differences; Substance-Related Disorders
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2017.11.019

•Study aim to determine if BDNF mediates alcohol seeking in a sex-specific manner.•Operant alcohol self-administration assessed in BDNF heterozygous (HET) and wildtype (WT) rats.•No significant sex or genotype effect in lever press acquisition, progressive ratio or extinction.•Alcohol-primed reinstatement higher in male vs. female WT but not BDNF HET; higher in female BDNF HET than female WT.•BDNF regulatory pathways are involved in sex differences in reinstatement of alcohol intake. Alcohol use disorder is a detrimental addictive disease that develops through prolonged ethanol exposure and regular intoxication. However, the changes in the underlying neurobiology leading to alcohol addiction remain unclear. Brain-Derived Neurotrophic Factor (BDNF) is implicated in substance abuse disorders including alcoholism. As the vast majority of previous animal model studies have concentrated on males only, the aim of this study was to determine whether endogenous BDNF mediates alcohol seeking in a sex-specific manner. We used an operant self-administration paradigm where the animals were trained in operant chambers to self-administer a 10% ethanol solution, and compared male and female BDNF heterozygous (HET) and wildtype (WT) rats. Over several weeks, the animals progressed through acquisition, progressive ratio, extinction, and reinstatement phases. There were no significant sex or genotype differences in the number of alcohol-paired lever presses during acquisition, progressive ratio and extinction. However, a significant difference between male and female WT rats following alcohol-primed reinstatement was completely absent in BDNF HET rats suggesting a role of BDNF in sex differences in alcohol seeking after abstinence. Female BDNF HET rats showed significantly higher number of alcohol-paired lever presses during reinstatement than female WT controls. These findings suggest that BDNF regulatory pathways are involved in sex differences in reinstatement of alcohol intake and emphasize the need to include both male and female animals to explore sex-specific interactions in addiction neurocircuitry.